rs202068829

Variant names:

• chrX-65518409-C-G
• rs202068829
• NM_031206.7:c.1505G>C
• LAS1L p.Arg502Pro

Your query was ambiguous. Multiple possible variants found:

• chrX-65518409-C-G
• chrX-65518409-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_031206.7(LAS1L):​c.1505G>C​(p.Arg502Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R502H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 24)
• Consequence: LAS1L NM_031206.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.450
• Publications: 3 publications found

Genes affected

LAS1L (HGNC:25726): (LAS1 like ribosome biogenesis factor) Enables RNA binding activity. Predicted to be involved in maturation of 5.8S rRNA and maturation of LSU-rRNA. Located in membrane. Part of MLL1 complex. Implicated in Wilson-Turner syndrome. [provided by Alliance of Genome Resources, Apr 2022]

LAS1L Gene-Disease associations (from GenCC):

• Wilson-Turner syndrome

  Inheritance: XL Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics
• spinal muscular atrophy with respiratory distress type 2

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet
• X-linked syndromic intellectual disability

  Inheritance: XL Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031206.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAS1L	NM_031206.7	MANE Select	c.1505G>C	p.Arg502Pro	missense	Exon 12 of 14	NP_112483.1	Q9Y4W2-1
	LAS1L	NM_001375328.1		c.1505G>C	p.Arg502Pro	missense	Exon 12 of 14	NP_001362257.1
	LAS1L	NM_001170649.2		c.1454G>C	p.Arg485Pro	missense	Exon 11 of 13	NP_001164120.1	Q9Y4W2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAS1L	ENST00000374811.8	TSL:1 MANE Select	c.1505G>C	p.Arg502Pro	missense	Exon 12 of 14	ENSP00000363944.3	Q9Y4W2-1
	LAS1L	ENST00000374807.9	TSL:1	c.1454G>C	p.Arg485Pro	missense	Exon 11 of 13	ENSP00000363940.5	Q9Y4W2-2
	LAS1L	ENST00000867035.1		c.1547G>C	p.Arg516Pro	missense	Exon 12 of 14	ENSP00000537094.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.082	T
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.45
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.15
Sift	Benign	0.20	T
Sift4G	Benign	0.16	T
Varity_R		0.60
gMVP		0.82
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs202068829;

hg19: chrX-64738289;